Synthesis of Cyclo[<i>b</i>]fused Carbazoles via SnCl₄‑Mediated Domino Reaction of 2‑Indolylmethylpivalates with Arenes and Heteroarenes

A straightforward synthesis of aryl and heteroaryl-annulated cyclo­[<i>b</i>]­carbazoles has been developed via SnCl₄-mediated one-pot arylation, cyclization and aromatization reaction sequence from 3-acetyl/aroyl-2-pivaloyloxymethylindoles. The starting material is easily accessible from commercially available 2-methylindole via Friedel–Crafts acylation, bromination and pivaloylation. Remarkably, electron withdrawing/donating aroyl units including heterocyclic systems are well tolerated in the present domino reaction protocol. Furthermore, this methodology could be extended to the synthesis of dibenzofurocarbazole via bis-annulation of 2,5-bis­(2-pivaloyloxymethyl)­pyrrole

Synthesis of Cyclo[<i>b</i>]fused Carbazoles via SnCl₄‑Mediated Domino Reaction of 2‑Indolylmethylpivalates with Arenes and Heteroarenes

A straightforward synthesis of aryl and heteroaryl-annulated cyclo­[<i>b</i>]­carbazoles has been developed via SnCl₄-mediated one-pot arylation, cyclization and aromatization reaction sequence from 3-acetyl/aroyl-2-pivaloyloxymethylindoles. The starting material is easily accessible from commercially available 2-methylindole via Friedel–Crafts acylation, bromination and pivaloylation. Remarkably, electron withdrawing/donating aroyl units including heterocyclic systems are well tolerated in the present domino reaction protocol. Furthermore, this methodology could be extended to the synthesis of dibenzofurocarbazole via bis-annulation of 2,5-bis­(2-pivaloyloxymethyl)­pyrrole

Synthesis of Cyclo[<i>b</i>]fused Carbazoles via SnCl₄‑Mediated Domino Reaction of 2‑Indolylmethylpivalates with Arenes and Heteroarenes

A straightforward synthesis of aryl and heteroaryl-annulated cyclo­[<i>b</i>]­carbazoles has been developed via SnCl₄-mediated one-pot arylation, cyclization and aromatization reaction sequence from 3-acetyl/aroyl-2-pivaloyloxymethylindoles. The starting material is easily accessible from commercially available 2-methylindole via Friedel–Crafts acylation, bromination and pivaloylation. Remarkably, electron withdrawing/donating aroyl units including heterocyclic systems are well tolerated in the present domino reaction protocol. Furthermore, this methodology could be extended to the synthesis of dibenzofurocarbazole via bis-annulation of 2,5-bis­(2-pivaloyloxymethyl)­pyrrole

Synthesis and Biological Evaluation of Calothrixins B and their Deoxygenated Analogues

A series of calothrixin B (<b>2</b>) analogues bearing substituents at the ‘E’ ring and their corresponding deoxygenated quinocarbazoles lacking quinone unit were synthesized. The cytotoxicities of calothrixins <b>1</b>, <b>2</b>, and <b>15b</b>–<b>p</b> and quinocarbazole analogues were investigated against nine cancer cell lines. The quinocarbazoles <b>21a</b> and <b>25a</b> inhibited the catalytic activity of human topoisomerase II. The plasmid DNA cleavage abilities of calothrixins <b>1</b>, <b>2</b>, and <b>15b</b>–<b>p</b> identified compound <b>15h</b> causing DNA cleavage comparable to that of calothrixin A (<b>1</b>). Calothrixin A (<b>1</b>), 3-fluorocalothrixin <b>15h</b> and 4-fluoroquinocarbazole <b>21b</b> induced extensive DNA damage followed by apoptotic cell death. Spectral and plasmid unwinding studies demonstrated an intercalative mode of binding for quinocarbazoles. We identified two promising drug candidates, the 3-fluorocalothrixin B <b>15h</b> with low toxicity in animal model and its deoxygenated derivative 4-fluoroquinocarbazole <b>21b</b> as having potent cytotoxicity against NCI-H460 cell line with a GI₅₀ of 1 nM